Clinical colorectal cancer最新文献

{"title":"Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme","authors":"John C. Taylor ,&nbsp;Dermot Burke ,&nbsp;Lene H. Iversen ,&nbsp;Rebecca J. Birch ,&nbsp;Paul J. Finan ,&nbsp;Mark M. Iles ,&nbsp;Philip Quirke ,&nbsp;Eva J.A. Morris ,&nbsp;YCR BCIP Study Group","doi":"10.1016/j.clcc.2024.05.013","DOIUrl":"10.1016/j.clcc.2024.05.013","url":null,"abstract":"<div><h3>Background</h3><div>The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England.</div></div><div><h3>Method</h3><div>We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme.</div></div><div><h3>Results</h3><div>In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average.</div></div><div><h3>Conclusion</h3><div>Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 382-391.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comparison of Cellular Immune Response and Immunological Biomarkers in Laparoscopic Surgery for Colorectal Cancer and Benign Disorders","authors":"Line Nederby ,&nbsp;Natacha Dencker Trabjerg ,&nbsp;Anja Bjørnskov Andersen ,&nbsp;Jan Lindebjerg ,&nbsp;Torben Frøstrup Hansen ,&nbsp;Hans Bjarke Rahr","doi":"10.1016/j.clcc.2024.05.012","DOIUrl":"10.1016/j.clcc.2024.05.012","url":null,"abstract":"<div><h3>Background</h3><div>Surgical trauma causes immune impairment, but it is largely unknown whether surgery for cancer and benign diseases instigate comparable levels of immune inhibition. Here, we compared the impact of laparoscopic surgery on immunological biomarkers in patients with colorectal cancer (CRC) and ventral hernia (VH).</div></div><div><h3>Methods</h3><div>Natural Killer cell activity (NKA), leukocyte subsets, and soluble programmed death ligand 1 (sPD-L1) were measured in blood samples collected from CRC (n = 29) and VH (n = 9) patients preoperatively (PREOP) and on postoperative day (POD) 1, 3-6, 2 weeks and 3 months. NKA was evaluated by the NK Vue assay that uses the level of IFNγ as a surrogate marker of NKA. Normal NKA was defined as IFNγ &gt; 250 pg/mL and low NKA was defined as IFNγ &lt; 250 pg/mL.</div></div><div><h3>Results</h3><div>The CRC cohort was classified into either PREOP_LOW having preoperative low NKA or PREOP_HIGH having preoperative normal NKA. The median NKA of the PREOP_LOW subset was only in the normal range in the POD3 months sample, whereas median NKA of the PREOP_HIGH subset and the VH cohort were only low in the POD1 sample. While PREOP_LOW differed from VH in the PREOP-, POD1-, and POD3-6 samples (<em>P</em> =.0006, <em>P</em> = .0181, and <em>P</em> = .0021), NKA in PREOP_HIGH and VH differed in the POD1 samples (<em>P</em> = .0226). There were no apparent differences in the distribution of leukocyte subsets in the perioperative period between the cohorts.</div></div><div><h3>Conclusion</h3><div>CRC patients with preoperative normal NKA and VH patients showed the same pattern of recovery in NKA, while the CRC subset with preoperative low NKA seemed to experience prolonged NK cell impairment. As low NKA is associated with recurrence, preoperative level of NKA may identify patients who will benefit from immune-enhancing therapy in the perioperative period.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 372-381.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Adjuvant Chemotherapy on Oncologic Outcomes in Patients With Stage ⅡA Rectal Cancer Above the Peritoneal Reflection Who Did Not Undergo Preoperative Chemoradiotherapy","authors":"Hyo Seon Ryu ,&nbsp;Jong Lyul Lee ,&nbsp;Chan Wook Kim ,&nbsp;Yong Sik Yoon ,&nbsp;In Ja Park ,&nbsp;Seok-Byung Lim ,&nbsp;Yong Sang Hong ,&nbsp;Tae Won Kim ,&nbsp;Chang Sik Yu","doi":"10.1016/j.clcc.2024.05.011","DOIUrl":"10.1016/j.clcc.2024.05.011","url":null,"abstract":"<div><h3>Purpose</h3><div><span>This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper </span>rectal cancer and to investigate whether AC is associated with improved survival outcomes.</div></div><div><h3>Methods</h3><div><span>This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative </span>chemoradiotherapy<span><span> between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, </span>perineural invasion, resection margin involvement, and &lt; 12 lymph nodes harvested.</span></div></div><div><h3>Results</h3><div><span>Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs</span><em>.</em> 84.6%, <em>P</em> = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs<em>.</em> 64.1%, <em>P</em> = .01) and 5-year OS (88.8% vs<em>.</em> 69.0%, <em>P</em> = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged &gt; 65 years.</div></div><div><h3>Conclusion</h3><div>AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 392-401"},"PeriodicalIF":3.3,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141574541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemotherapy Rechallenge or Reintroduction Compared to Regorafenib or Trifluridine/Tipiracil for Pretreated Metastatic Colorectal Cancer Patients: A Propensity Score Analysis of Treatment Beyond Second Line (Proserpyna Study)","authors":"M.A. Calegari ,&nbsp;I.V. Zurlo ,&nbsp;E. Dell'Aquila ,&nbsp;M. Basso ,&nbsp;A. Orlandi ,&nbsp;M. Bensi ,&nbsp;F. Camarda ,&nbsp;A. Anghelone ,&nbsp;C. Pozzo ,&nbsp;I. Sperduti ,&nbsp;L. Salvatore ,&nbsp;D. Santini ,&nbsp;D.C. Corsi ,&nbsp;E. Bria ,&nbsp;G. Tortora","doi":"10.1016/j.clcc.2024.06.002","DOIUrl":"10.1016/j.clcc.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><div><span>The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, </span>REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.</div></div><div><h3>Patients and methods</h3><div>PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.</div></div><div><h3>Results</h3><div>Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 <em>vs.</em> 6.5 months), PFS (6.1 <em>vs.</em> 3.5 months) and RR (28.6% <em>vs.</em> 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.</div></div><div><h3>Conclusions</h3><div>Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"24 1","pages":"Pages 1-10.e4"},"PeriodicalIF":3.3,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncological Outcomes and Response Rate After Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Network Meta-Analysis Comparing Induction vs. Consolidation Chemotherapy vs. Standard Chemoradiation","authors":"Sergei Bedrikovetski ,&nbsp;Luke Traeger ,&nbsp;Warren Seow ,&nbsp;Nagendra N. Dudi-Venkata ,&nbsp;Sudarsha Selva-Nayagam ,&nbsp;Michael Penniment ,&nbsp;Tarik Sammour","doi":"10.1016/j.clcc.2024.06.001","DOIUrl":"10.1016/j.clcc.2024.06.001","url":null,"abstract":"<div><div>TNT is now considered the preferred option for stage II-III locally advanced rectal cancer (LARC). However, the prognostic benefit and optimal sequence of TNT remains unclear. This network meta-analysis (NMA) compared short- and long-term outcomes amongst patients with LARC receiving total neoadjuvant therapy (TNT) as induction (iTNT) or consolidation chemotherapy (cTNT) with those receiving neoadjuvant chemoradiation (nCRT) alone. A systematic literature search was performed between 2012 and 2023. A Bayesian NMA was conducted using a Markov Chain Monte Carlo method with a random-effects model and vague prior distribution to calculate odds ratios (OR) with 95% credible intervals (CrI). The surface under the cumulative ranking (SUCRA) curves were used to rank treatment(s) for each outcome. In total, 11 cohorts involving 8360 patients with LARC were included. There was no significant difference in disease-free survival (DFS) and overall survival (OS) amongst the 3 treatments. Compared with nCRT, both cTNT (OR 2.36; 95% CrI, 1.57-3.66) and iTNT (OR 1.99; 95% CrI, 1.44-2.95) significantly improved complete response (CR) rate. Notably, cTNT ranked as the best treatment for CR (SUCRA 0.90) and iTNT as the best treatment for 3-year DFS and OS (SUCRA 0.72 and 0.87, respectively). Both iTNT and cTNT strategies significantly improved CR rates compared with nCRT. cTNT was ranked highest for CR rates, while iTNT was ranked highest for 3-year survival outcomes. However, no other significant differences in DFS, OS, sphincter-saving surgery, R0 resection and postoperative complications were found amongst the treatment groups.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 326-336.e9"},"PeriodicalIF":3.3,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141411062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment of Metastatic Biliary Cancers With Irinotecan and 5-Fluorouracil Based Chemotherapy After Platinum/Gemcitabine Progression: A Systematic Review and Meta-Analysis","authors":"Ioannis A. Voutsadakis ,&nbsp;Stefania Kokkali ,&nbsp;Antonia Digklia","doi":"10.1016/j.clcc.2024.05.009","DOIUrl":"10.1016/j.clcc.2024.05.009","url":null,"abstract":"<div><h3>Background</h3><div>Biliary tract carcinomas<span><span> are cancers that, despite a lower prevalence compared with other gastrointestinal cancers, represent a significant </span>public health burden due to their aggressiveness. The metastatic stage of the disease is highly lethal and difficult to treat. Options of systemic therapies, especially beyond the first line are few and less well established.</span></div></div><div><h3>Methods</h3><div><span>We performed a systematic review<span><span> of literature databases to identify studies of the combination of irinotecan and 5-fluorouracil (5-FU) based chemotherapy as treatment of metastatic biliary tract carcinomas in second line, after first line treatment with platinum/gemcitabine chemotherapy. Both prospective and retrospective designs were admissible. A meta-analysis of identified studies to determine summary estimates for overall response rate (ORR), disease control rate (DCR), </span>progression free survival (PFS) and </span></span>overall survival (OS) was also performed.</div></div><div><h3>Results</h3><div>The search was performed in PubMed/Medline and in Embase databases and identified a total of 339 articles. Manual review resulted in 8 articles that were eligible for inclusion in the meta-analysis. Second line irinotecan/5-FU based combinations produced an ORR of 9.1% (95% CI, 5.5%-12.6%) and DCR of 43.3% (95% CI, 15.8%-70.8%). Summary PFS and OS were 2.7 months (95% CI, 2.3-3.1 months) and 6.8 months (95% CI, 5.6-8.0 months), respectively. Treatments appeared to be feasible with adverse effect profiles as expected from the combination.</div></div><div><h3>Conclusion</h3><div>A moderate activity of second line irinotecan/5-FU based chemotherapy was observed in this meta-analysis. The combination is an option for patients progressing on platinum/gemcitabine chemotherapy, who maintain a sufficient general status to receive active therapy. This combination may also serve as the control arm of second line trials with new targeted agents.</div></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 4","pages":"Pages 318-325.e1"},"PeriodicalIF":3.3,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141278014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab Plus mFOLFOX7 or FOLFIRI for Microsatellite Stable/Mismatch Repair-Proficient Metastatic Colorectal Cancer: KEYNOTE-651 Cohorts B and D","authors":"Richard Kim ,&nbsp;Mustapha Tehfe ,&nbsp;Petr Kavan ,&nbsp;Jorge Chaves ,&nbsp;Jeremy S. Kortmansky ,&nbsp;Eric X. Chen ,&nbsp;Christopher H. Lieu ,&nbsp;Lucas Wong ,&nbsp;Marwan Fakih ,&nbsp;Kristen Spencer ,&nbsp;Qing Zhao ,&nbsp;Raluca Predoiu ,&nbsp;Chenxiang Li ,&nbsp;Pierre Leconte ,&nbsp;David Adelberg ,&nbsp;E. Gabriela Chiorean","doi":"10.1016/j.clcc.2024.03.001","DOIUrl":"10.1016/j.clcc.2024.03.001","url":null,"abstract":"<div><h3>Background</h3><p>The phase 1b KEYNOTE-651 study evaluated pembrolizumab plus chemotherapy in microsatellite stable or mismatch repair-proficient metastatic colorectal cancer.</p></div><div><h3>Patients and Methods</h3><p>Patients with microsatellite stable or mismatch repair-proficient metastatic colorectal cancer received pembrolizumab 200 mg every 3 weeks plus 5-fluorouracil, leucovorin, oxaliplatin (previously untreated; cohort B) or 5-fluorouracil, leucovorin, irinotecan (previously treated with fluoropyrimidine plus oxaliplatin; cohort D) every 2 weeks. Primary end point was safety; investigator-assessed objective response rate per RECIST v1.1 was secondary and biomarker analysis was exploratory.</p></div><div><h3>Results</h3><p>Thirty-one patients were enrolled in cohort B and 32 in cohort D; median follow-up was 30.2 and 33.5 months, respectively. One dose-limiting toxicity (grade 3 small intestine obstruction) occurred in cohort D. In cohort B, grade 3 or 4 treatment-related adverse events (AEs) occurred in 18 patients (58%), most commonly neutropenia and decreased neutrophil count (n = 5 each). In cohort D, grade 3 or 4 treatment-related AEs occurred in 17 patients (53%), most commonly neutropenia (n = 7). No grade 5 treatment-related AEs occurred. Objective response rate was 61% in cohort B (<em>KRAS</em> wildtype: 71%; <em>KRAS</em> mutant: 53%) and 25% in cohort D (<em>KRAS</em> wildtype: 47%; <em>KRAS</em> mutant: 6%). In both cohorts, PD-L1 combined positive score and T-cell-inflamed gene expression profiles were higher and HER2 expression was lower in responders than nonresponders. No association between tumor mutational burden and response was observed.</p></div><div><h3>Conclusion</h3><p>Pembrolizumab plus 5-fluorouracil, leucovorin, oxaliplatin/5-fluorouracil, leucovorin, irinotecan demonstrated an acceptable AE profile. Efficacy data appeared comparable with current standard of care (including by <em>KRAS</em> mutation status). Biomarker analyses were hypothesis-generating, warranting further exploration.</p></div><div><h3>ClinicalTrials.gov Identifier</h3><p>ClinicalTrials.gov; NCT03374254</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 118-127.e6"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review","authors":"Eric D. Miller ,&nbsp;Brett G. Klamer ,&nbsp;Jordan M. Cloyd ,&nbsp;Timothy M. Pawlik ,&nbsp;Terence M. Williams ,&nbsp;Kathryn E. Hitchcock ,&nbsp;Paul B. Romesser ,&nbsp;Harvey J. Mamon ,&nbsp;Kimmie Ng ,&nbsp;Sepideh Gholami ,&nbsp;George J. Chang ,&nbsp;Christopher J. Anker","doi":"10.1016/j.clcc.2024.01.004","DOIUrl":"10.1016/j.clcc.2024.01.004","url":null,"abstract":"<div><h3>Background</h3><p>A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT).</p></div><div><h3>Materials and Methods</h3><p>An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions.</p></div><div><h3>Results</h3><p>Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT.</p></div><div><h3>Conclusions</h3><p>Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 160-173"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1533002824000045/pdfft?md5=b73b78ab7b7a93a7f10dda6c37cb59c4&pid=1-s2.0-S1533002824000045-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139646133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab Plus Binimetinib With or Without Chemotherapy for MSS/pMMR Metastatic Colorectal Cancer: Outcomes From KEYNOTE-651 Cohorts A, C, and E","authors":"Eric X. Chen ,&nbsp;Petr Kavan ,&nbsp;Mustapha Tehfe ,&nbsp;Jeremy S. Kortmansky ,&nbsp;Michael B. Sawyer ,&nbsp;E. Gabriela Chiorean ,&nbsp;Christopher H. Lieu ,&nbsp;Blase Polite ,&nbsp;Lucas Wong ,&nbsp;Marwan Fakih ,&nbsp;Kristen Spencer ,&nbsp;Jorge Chaves ,&nbsp;Chenxiang Li ,&nbsp;Pierre Leconte ,&nbsp;David Adelberg ,&nbsp;Richard Kim","doi":"10.1016/j.clcc.2024.03.002","DOIUrl":"10.1016/j.clcc.2024.03.002","url":null,"abstract":"<div><h3>Background</h3><p>Cohorts A, C, and E of the phase Ib KEYNOTE-651 study evaluated pembrolizumab + binimetinib ± chemotherapy in microsatellite stable/mismatch repair-proficient metastatic colorectal cancer.</p></div><div><h3>Patients and Methods</h3><p>Patients received pembrolizumab 200 mg every 3 weeks plus binimetinib 30 mg twice daily alone (cohort A; previously treated with any chemotherapy) or with 5-fluorouracil, leucovorin, oxaliplatin (cohort C; previously untreated) or 5-fluorouracil, leucovorin, irinotecan (cohort E; previously treated with 1 line of therapy including fluoropyrimidine + oxaliplatin-based regimen) every 2 weeks. Binimetinib dose-escalation to 45 mg twice daily was planned in all cohorts using a modified toxicity probability interval design (target dose-limiting toxicity [DLT], 30%). The primary endpoint was safety; investigator-assessed objective response rate was secondary.</p></div><div><h3>Results</h3><p>In cohort A, 1/6 patients (17%) had DLTs with binimetinib 30 mg; none occurred in 14 patients with 45 mg. In cohort C, 3/9 patients (33%) had DLTs with binimetinib 30 mg; dose was not escalated to 45 mg. In cohort E, 1/5 patients (20%) had DLTs with binimetinib 30 mg; 5/10 patients (50%) had DLTs with 45 mg. Enrollment was stopped in cohort E binimetinib 45 mg and deescalated to 30 mg; 2/4 additional patients (50%) had DLTs with binimetinib 30 mg (total 3/9 [33%] had DLTs with binimetinib 30 mg). Objective response rate was 0% in cohort A, 9% in cohort C, and 15% in cohort E.</p></div><div><h3>Conclusion</h3><p>Per DLT criteria, binimetinib + pembrolizumab (cohort A) was tolerable, binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, oxaliplatin (cohort C) did not qualify for binimetinib dose escalation to 45 mg, and binimetinib + pembrolizumab + 5-fluorouracil, leucovorin, irinotecan (cohort E) required binimetinib dose reduction from 45 to 30 mg. No new safety findings were observed across cohorts. There was no apparent additive efficacy when binimetinib + pembrolizumab was added to chemotherapy. Data did not support continued enrollment in cohorts C and E.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 183-193"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis","authors":"Soo Young Oh ,&nbsp;Chan Wook Kim ,&nbsp;Seonok Kim ,&nbsp;Min Hyun Kim ,&nbsp;Young Il Kim ,&nbsp;Jong Lyul Lee ,&nbsp;Yong Sik Yoon ,&nbsp;In Ja Park ,&nbsp;Seok-Byung Lim ,&nbsp;Chang Sik Yu","doi":"10.1016/j.clcc.2024.04.002","DOIUrl":"10.1016/j.clcc.2024.04.002","url":null,"abstract":"<div><h3>Microabstract</h3><p>This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types.</p></div><div><h3>Background</h3><p>This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes.</p></div><div><h3>Materials and Methods</h3><p>A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders.</p></div><div><h3>Results</h3><p>Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, <em>P</em> &lt; .001) and overall survival (HR = 1.853, <em>P</em> = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, <em>P</em> = .028) and overall survival (HR = 1.732, <em>P</em> = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types.</p></div><div><h3>Conclusion</h3><p>Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.</p></div>","PeriodicalId":10373,"journal":{"name":"Clinical colorectal cancer","volume":"23 2","pages":"Pages 135-146.e3"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140762548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}